FR2655426A1 - - Google Patents

Abstract

An automatic immunity analysis apparatus, comprising reaction vessels (1) arranged in series, a transport device for said reaction vessels, a first dividing device (P1) which divides and loads a sample into each of said reaction vessels, a first stirring device (P2, B1) which splits and charges an antibody insoluble magnetic solution into each of said reaction vessels, a second splitting device (P4) which splits and charges a stroma solution in each of said reaction vessels, an absorption device (M1), a first cleaning device (P3), a second agitation device (B2) which divides and agitates a solution of antibody labeled with an enzyme, a second adsorption device (M2), a second cleaning device (G2), a third dividing device (P6) which divides and charges a reaction stop solution, a measuring device (9) which optically measures an ech antillon in each of said reaction vessels and in an optical measurement position, and a third cleaning device (F).

Description

The present invention relates to an automatic analysis apparatus for

  immunity and in particular an automatic immunity analysis device suitable for the method of measuring oxygen immunity (designated enzyme-linked immunoassay method

  below by EIA method) using the antigen reaction-

  antibody. The EIA method has been used recently as a method of measuring immunity using the antigen-antibody reaction,

well known in the prior art.

  The reaction of the EIA method is so sensitive and so pre-

  states that the method is used to perform the following analyzes, for example CEA, Iron, 92-M, Ig E, TSH, T 3, T 4, AFP, CA-50, etc. This EIA method described above is classified as EIA pearl method and EIA coated method, etc., as it

  is known in the prior art; in the first method, the anti

  body is sensitized on the surface of the spherical beads, while in the second method it is coated on the surface of the

cell membran.

  However, in these EIA methods known in the prior art

  laughing, it is required to add a non-antibody solution, a stroma solution, a reaction stop solution, etc., from time to time in accordance with the progress of the reaction. products is very complicated However, the reaction time duration of such an inspection is very long since a long time is spent until the final result of the inspection is available These problems associated with conventional EIA methods are disadvantageous for the

practical applications.

  In order to resolve the problems associated with techno-

  conventional logies, the present invention provides an automatic immunity analysis device comprising reaction vessels arranged in series, a transport device for said reaction vessels, a first dividing device

  which sucks a sample in predetermined quantity in a posi-

  predetermined tion and divides and loads said sample into each of said containers, a first stirring device which divides and loads a magnetic solution insoluble in the antibody

  in each of said reaction vessels containing said sample

  divided and loaded drum, a second dividing device which is provided after said first stirring device and which divides and loads a stroma solution into each of said containers, a

  adsorption device which adsorbs said magnetic solution

  tick insoluble in the antibody on a surface of the interior wall

  of each of said reaction vessels, a first available

  cleaning agent which rejects a reaction solution out of each of said reaction vessels while said magnetic solution insoluble in the antibody is still adsorbed on the internal wall of each of said reaction vessels, then cleans each of said vessels, a second device for stirring which divides and shakes an enzyme labeled antibody solution, a second adsorption device which adsorbs said antibody-insoluble magnetic solution on a surface of the inner wall of each of said reaction vessels, a second device cleaning agent which rejects a reaction solution out of each of said reaction vessels while said magnetic solution insoluble in the antibody is still adsorbed on the inner wall of each of said reaction vessels, and which then cleans each of said vessels, a third device divider that divides and loads a stop solution of the reaction, a measuring device which optically measures a sample in each of said reaction vessels in an optical measuring position, and a third cleaning device which cleans the interior of each of said

  reaction vessels after completion of a measurement.

  A second aspect of the present invention consists in

  provide the automatic immunity analyzer specified above

  above, wherein said first stirring device for an antibody-insoluble magnetic solution comprises a reagent container holder which is rotated by a driving apparatus, a rotating body which is engaged with a retention hole of said reagent container holder in a freely rotatable manner, a fixed gear body on a peripheral surface of which are cut gear teeth, a gear body which is engaged with the gear teeth a gear of said fixed gear body and which drives said rotary body when said reagent container holder is rotating, and protruding bodies which are raised in predetermined intervals along a peripheral surface of said fixed gear body, apparatus according to which a magnetic solution insoluble in the antibody housed in said rotary body is rotated and stirred when said reagent container is in rotation, and housed in said rotating body in such a way that said magnetic solution insoluble in the antibody is shaken and agitated with the help

said protruding bodies.

  Yet another object of the present invention is to provide an automatic immunity analysis apparatus specified in the first object previously of the present invention, wherein said first agitation device which divides and charges a magnetic solution insoluble in the antibody contained in each of said reagent containers in each of said reaction containers comprises an agitator arm and a pipette arm, said agitator arm is equipped with one of said agitation bodies in an intermediate portion and with a supported drain pipette on a top portion and having the shape of a flat L, and said pipette arm is equipped with a dividing pipette in an end portion, while said stirring pipette is in an end portion, while the agitator arm and the pipette arm are supported coaxially; apparatus in which said stirring rod, said drain pipette and said dividing pipette are cleaned in a predetermined position; then only the division pipette is in rotation and pushes the drain pipette and moves to the suction position of the solution; and said emptying pipette returns to its place when said dividing pipette draws up the magnetic solution insoluble in the antibody and

  returns to said cleaning position.

  In accordance with another object of the invention, an automatic immunity analysis device produced according to the invention is an automatic immunity analysis device specified in the first object mentioned above of the invention, wherein said first and second cleaning devices for cleaning the interior walls of said reaction vessels comprise an L-shaped arm fixed on a shaft at one end, a solution suction pipette mounted on a top portion of said arm, a cleaning water supply pipette and a stirrer body; apparatus according to which said solution suction pipette, said cleaning water supply pipette and said agitation body are mounted on a top portion of said arm in a sequential order so as to form a downstream side up to an upstream side in the direction of transport of the reaction vessels in which said pipettes and said

agitation bodies are inserted.

  On The attached drawings Figure 1 is a plan view generally showing the

  entire composition of an embodiment of the analysis apparatus

  automatic lysis of immunity in accordance with this invention

  tion. Figure 2 is a sectional view showing the structure of a stirring device for shaking and shaking a container of

  reagent containing a magnetic solution insoluble in

body.

  Figure 3 is a partially cutaway view of the arrangement

  agitation sitive shown in Figure 2.

  Figure 4 is a front view showing the composition

tion of a rotating body.

  Figure 5 is a side view showing the composition

of said rotary body.

  Figure 6 is a sectional view showing another embodiment of the stirring device for shaking and shaking a reagent container containing a magnetic solution

insoluble in the antibody.

  FIG. 7 is a descriptive plan view of a drain pipette device which aspirates and rejects an magnetic solution insoluble in the antibody in a reaction vessel 1 while the said magnetic solution insoluble in the antibody is still adsorbed on a surface interior of the reaction vessel using a first magnetic body, a third device to

  pipette to divide and load a stroma solution and a solution

  tion of enzyme-labeled antibody and a stirring device for agitating the interior of reaction vessel 1 in which the stroma solution and the antibody-labeled solution

  enzyme were loaded after division.

  Figure 8 is a sectional view showing the composition

  a drain pipette device and said agitator device

tion shown in Figure 7.

  Figures 9 (A) to (C) are descriptive plan views showing sequentially the operation of the drain pipette device, The third pipette device and the device

Figure 7.

  FIG. 10 is a descriptive plan view of the composition

  tion of a cleaning and stirring device.

  Figure 11 is an oblique view showing the composition

  of the cleaning and stirring device of FIG. 10.

  Figure 12 is a block diagram showing sequen-

  the operating procedures of an automatic analysis device

  immunity tick according to the embodiment of the

present invention.

  Automatic immunity analyzer showed

  in the drawings relates to the 2-stage type.

  The 2-step type of the present application is defined by a system in which, before a labeled antibody solution

  by an enzyme be loaded into a reaction vessel, the container

  pient is cleaned to remove a magnetic solution insoluble in the residual antibody The 1-step type is a system in which the cleaning process provided for in the 2-step type is

omitted.

  Referring to Figure 1, the embodiment of an automatic immunity analysis device A comprises a plurality (72 pieces in this embodiment) of reaction vessels 11 arranged in the form of '' a loop, a driving apparatus for transporting these reaction vessels (not illustrated), a sampling pipette device P1 which sucks

  a predetermined amount of a sample at a sample position

  tillonnage b and divides and loads the sample into one of said reaction vessels 1, which is placed in position "a", a first pipette device P 2 which divides and loads a magnetic solution insoluble in the antibody in the reaction container filled with said sample, an agitator device B1 which agitates the magnetic solution insoluble in the antibody divided and loaded into the reaction container 1, a second pipette device P 3 which divides and loads a cleaning solution 5 into the container reaction 1, a first magnetic body M 1 which adsorbs a magnetic body insoluble in the antibody m on the surface of the internal wall of the reaction vessel 1 in which the cleaning solution 5 has been additionally divided and charged, a device with a drain pipette H 1 which sucks in and rejects the magnetic solution insoluble in the antibody of the reaction vessel 1 while the insoluble magnetic body in the antibody m still remains adsorbed on the surface of the internal wall of the reaction vessel 1, a third pipette device P 4 which divides and loads a stroma solution, that is to say an antibody solution 6 marked with an enzyme in said reaction container 1 after the completion of the aspiration and rejection by the drain pipette device H 1, a stirring device B 2 which agitates the divided and charged stroma solution, that is that is to say the solution 6 of antibody labeled with an enzyme in the reaction vessel 1, magnetic bodies M 2, M 3, M 4 and M 5 which adsorb said magnetic body insoluble in the antibody on the surface of the wall

  reaction vessel 1 after completion of agitation

  tion by the agitator device B 2 and a magnetic body M 6 located in an optical measurement position S, cleaning and stirring devices Gi to G 3 which suck up and reject The so Magnetic solution inso Lub Le in the antibody of the reaction vessel 1 while the magnetic body is inso luble in the antibody is still adsorbed on the surface of the inner wall of reaction vessel 1 while also providing a cleaning solution in reaction vessel 1 from which L Said so Magnetic solution inso Lub Le in The antibody was rejected and with shaking The cleaning solution now loaded in The reaction container, a fourth pipette device P 5 which divides and loads a so Lution of stroma in The reaction container 1 after the completion of the stirring by the cleaning and stirring devices Gi to G 3, a stirring device B 3 which stirs the solution of stroma divided and charged in the reaction vessel 1, a fifth pipette device P 6 which divides and loads a reaction stop solution 8 after the stirring has been completed by the agitator device B 3, an optical measuring device 9 which optically measures L reaction state of a L Lon sample in the reaction container 1 to an optical measurement position, an indication device (not i L Glossy) which indicates an absorbance measured by the optical measurement device 9 on a printer or a CRT (cathode ray tube) etc, after an A / D conversion, and a cleaning device F which cleans the interior of the reaction vessel after

of measurement.

  Completion The drive device for transporting The reaction vessel 1 transports a p Lurality of said reaction vessels 1 intermittently step by step in the direction

  contrary to that of the needle Les of a watch of FIG. 1 sequenced

  tie L Lement to a predetermined position while heating The containers 1 to a predetermined temperature The step feed device rotates in the direction (contrary to this L Le of the acute L Les of a watch of Figure 1) à The direction of transport intermittently (clockwise in Figure 1) a number of steps less than 1 than the number of

  reaction vessels (71 steps, i.e. 3600 360/720).

  As summarized by Ltat, The reaction vessels 1 are intermittently transported clockwise in FIG. 1 container by container This device for transporting the reaction vessels comprises a stepping motor known in the art previous Of course it is possible according to the invention to replace the stepwise rotation control for said 3600 N (number of containers) by the stepwise rotation control of 360 + N (number of containers) At this time, the the sample in the reaction vessels 1 is heated to about 37 ° C. by a constant temperature device known from

prior art (not shown).

  At a sampling position "a", a quantity

  sample is drawn from a sample container

  til Lon 10 and divided and loaded into a reaction vessel 1.

  Twelve sample containers 10 are mounted on a sample cassette 12 and transported sequentially and

  linearly in position b by means of a transfer device

  wearing of sample containers (not illustrated) including a mechanism

  feeding system known from the prior art.

  Said magnetic solution insoluble in the antibody is housed in the reagent containers 3 arranged in the form of a loop inside a reagent holder 11 The stroma solution, that is to say the solution d antibody labeled with an enzyme is housed in the reagent containers 6 arranged according to

  the shape of a loop inside said reagent holder 11.

  At this time, the magnetic body m insoluble in the antibody of said magnetic solution insoluble in the antibody precipitates at the bottom of the containers when the containers are stationary due to the high specific weight of the magnetic body m insoluble in the antibody , leading to fluctuating measurement accuracy To avoid this, the magnetic solution insoluble in the antibody is

  stirred using the agitator 20.

  More explicitly, the magnetic solution inso-

  luble in the antibody housed inside the reagent containers 3 comprises fine magnetic particles known from the prior art (a diameter of about 2.6 μm) after fixing as an antibody In the stationary state, the weight specific for said magnetic solution insoluble in the antibody is so large that it precipitates in the bottom portion of the containers.

reagent 3.

  Said reagent holder 11 transports the reagent containers 3 and 6 containing a magnetic solution insoluble in the antibody and a solution of stroma, that is to say the solution of antibody labeled with an enzyme to the division portions. and loading of reagent c and d, respectively by means of a drive device not shown When the reagent containers 3 and 6 containing a magnetic solution insoluble in the antibody and a solution of stroma, that is to say say the enzyme labeled antibody solution arrive at these dividing and loading positions of reagents c and d respectively, said first pipette device P 2 and said third pipette device P 4 draw up predetermined amounts of a magnetic solution insoluble in antibody and stroma, that is to say the solution of antibody labeled with an enzyme, and divide and load said solutions into reaction vessels 1 transported in a po sition e division and loading of a magnetic solution insoluble in the antibody and in a position g of division and loading of an antibody solution labeled with an enzyme, respectively The bottles arranged on said reagent holder 11 are previously placed in predetermined positions each of which is stored in a

  CPU control device (central process).

  Said stirring device 20 which shakes and shakes the

  reagent containers 3 containing said insoluble magnetic solution

  luble in the antibody is shown in Figures 2 to 5 (for

  for convenience of description, illustration of container

  of reagent 6 is omitted from the reagent containers 3 and 6 held in the reagent holder 11) The stirring device 20 comprises a rotating body 21 loosely supporting a reagent container, said reagent holder 11 having the shape of a loop and supporting a plurality of rotary bodies 21 in a freely rotatable manner at predetermined intervals, a driving device 22 for rotating said reagent holder 11, a support body 23 for re-connecting said rotary body 21 with the holder reagent 11, a gear body 24 fixed to the support body 23, a fixed gear body 25 with gear teeth 25 a in engagement with the gear body 24, and solid bodies L 26 raised on the outer periphery of the fixed gear body 25 at interva L The predetermined The rotary body 21 is constructed with a U-shaped section as shown in Figure 2 and an inner diameter of a portion 3 a of Housing container Slightly larger than the outside diameter of a reagent container 3, so that a reagent container 3 can

  osci L Ler and move with a predetermined play.

  In the lower periphery of the rotary body 21, two openings 27 are provided to allow said body in surface L Lie 26 to advance and retract as shown in Figures 3 to 5, in angular spacings of 900 each De p The upper portion of the inner periphery of said rotary body 21, a

  p Lura Lité of springs 28 is mounted in Interva L Predeter-

  mined along the inner periphery of the rotating body 21 in order to maintain a container of reagent 3 substantially in the central portion of the rotating body 21, while remaining in contact

  elastic with the outer periphery of the reagent container 3.

  On the bottom portion of said rotary body 21 thus composed, a head portion 23 a of said support body 23 is in a L L lie in a freely rotatable manner while being in contact with the bottom portion of the reagent container 3 housed in said rotary body 21 on the outer periphery of said support body 23 said gear body 24 is fixed on the bottom portion of the rotary body 21 to an upper end portion of a

rotating way.

  The lower end portion of said support body 23 is rotatably inserted into the retaining hole 29 formed

in said reagent holder 11.

  The head portion 23a of said support body 23 constructed as described above is composed in such a way that the said reagent container 3 is laced in the rotating body 21 so that the axial centers of the container reagent 3 and the support body 23 may coincide nature L Lement while The head portion 23 has come into contact with a central portion Le

  of a portion slightly set back from the reaction vessel 3.

  The reagent holder 11 is fixed and composed in a way

  such as a reagent container 3 containing a so Lution magneti-

  that inso Lub Le in The antibody is transported in a position of division and loading of a predetermined reagent (not it Glossy) by means of a motor M, of a gear 22 fixed on the rotary shaft of the motor M and engaging with Gear teeth 30 a

  constructed in a lower portion of the reagent holder 11.

  When the reagent container 3 containing the so inso Lub le magnetic Lution in the antibody divided and loaded at this position of division and charge of reagent arrives, said first pipette device P 2 sucks said so inso Lub Le magnetic lution in L of the reagent container 3 at this position for dividing and loading reagent with a predetermined amount and dividing and loading it into the reaction container 1 A fixed gear body 25 having the shape of a circular disc is fixed on a support body 31 as shown in Figure 2 and arranged inside said support body 23 so that the gear 22 has built in a lower portion of the outer periphery

  could normally engage with said gear body 24.

  In an upper portion of the outer periphery of said fixed gear body 25, Said bodies in lie L Lie 26 are arranged in elevation in interva L The predetermined Along

the circumferential direction L Le.

  Therefore, the insoluble magnetic solution in the antibody in the reagent container 3 housed in the rotating body 21 is rotated and agitated when said gear body 24 is engaged with said gear 22 has of the fixed gear body. While the reagent carrier 11 is rotated and transported to the dividing and loading position as described above. Furthermore, the reagent container 3 housed in said rotating body 21 is tilted and shaken inside the rotating body. 21 When it comes into contact with the body in sai L Lie 26 making sai L Lie on the body with fixed gear during the rotation and transport operation described above Consequently, each time that the reagent holder 11 is driven in rotation by the drive device 22, the reagent container 3 held by the rotary body 21 is rotated and shaken, so that the magnetic so in luble in L ' antibodies in this reagent container

  3 is shaken and shaken effectively.

  This stirring device 20 can also be composed in the following manner If reference is made to FIG. 6, an axis x

  a support body 23 supported with free rotation on the holder

  reagent 11 is deflected from the y axis of the reagent container 3 when it is housed in the rotary body 21 An auxiliary rotation body 32 is mounted between the head portion 23a of the support body 23 and the bottom portion of the reagent container 3 and is engaged with the head portion 23a of the support body 23 with a hollow portion 33 provided in a central rotation portion of said auxiliary rotation body 32 In addition, a central rotation projection 34 is provided in contact with a central portion of a hollow portion 3 b of said reagent container 3, projecting from the upper surface of said auxiliary rotation body 32, and projecting, eccentrically, relative to said portion

  hollow 33 In addition, several projections 35 are provided in elevation

  tion on the upper portion of the inner surface of the rotary body 21 in place of the springs 28 of said embodiment to

predetermined intervals.

  Thus, the reagent container 3 housed in the rotary body 21 is rotated eccentrically by the actions of the support body 23 and the auxiliary rotation body 32 In addition, said reagent container 3 remains in contact with the body in projection 26 mounted and elevated on said fixed gear body Thus, the container 3 oscillates in the rotary body 21 and is

thus shaken and agitated.

  Of course, said reagent container 6 is held in a holding hole provided on the outside of the rotary body 21 of the fixed gear body 25 although this is not illustrated in FIGS. 2 to 6 A solution of stroma, this i.e. an enzyme labeled antibody solution housed in said reagent container 6 is agitated when the gear body

fixed 25 is rotated.

  When the division and loading of the magnetic solution insoluble in the antibody in the reaction container 1 located in the position e of division and loading of the magnetic solution insoluble in the antibody are thus complete, said reaction container 1 is transported from the upstream side - by a step equivalent to a container using the drive device In this position, the sample (mixed solution of the sample and the magnetic solution insoluble in the antibody) is agitated using the device

Bi agitator.

  After that, said reaction container 1 is transported to a position f for dividing and loading the cleaning solution in which the cleaning solution 5 is divided and loaded into the reaction container 1 using a second device. pipette P 3 Said second pipette device P 3 comprises, similarly to the composition of conventional pipette devices known in the prior art, an arm of which one end is supported on the shaft, a pipette arranged at the other end of said arm, a pump which is connected to and which communicates with said pipette and draws a predetermined quantity of cleaning solution 5 and discharges it into the reaction vessel 1 and drives (not shown) which rotate and which control said arm from a predetermined position at each part to another position within a predetermined time while controlling the elevation and the abai ssement of the arm at each position The reaction vessel 1 in which the cleaning solution is divided and loaded is transported in

  a position g for dividing and loading the anti-solution

  body marked by an enzyme where there is a first magnetic body

  Mi to adsorb the magnetic body m insoluble in the anti

  body in the reaction vessel 1 on the surface of the inner wall of said reaction vessel 1, a drain pipette device Hi which aspirates and rejects the solubility Magnetic solution insolub Le in the antibody in the reaction vessel 1 while the magnetic body insoluble in antibody m is still adsorbed on the inner surface of the reaction vessel 1, a third pipette device P 4 which divides and loads a stroma solution, i.e. a solution of labeled antibody by an enzyme 6 in said reaction vessel 1 after the above, and a stirring device B 2 which shakes The stroma solution, that is to say the solution 6 of antibodies labeled with a divided enzyme * and loaded into the reaction vessel 1 The third pipette device P 4 comprises, with reference to FIG. 7, a pipette arm 41 one end of which is supported by the shaft 40,

  a dividing and loading pipette 42 provided at the other end

  mite from said pipette arm 41, a pump (not shown) which is

  connected to and which communicates with the division and charging pipette

  42 and draws a predetermined quantity of a solution and discharges it into the reaction vessel 1, and each driving device (not illustrated) which rotates and which controls said pipette arm 41 from the position g of division and loading of the enzyme-labeled antibody solution at the suction position of the antibody-labeled antibody solution

  enzyme via a cleaning position within predetermined times.

  The measurement of a quantity using the third pipette device P 4 is done by filling with water in the suction system and then suction and measurement of the water while keeping the water isolated from the reagent by l Then only the reagent is discharged while cleaning the inside of the pipette by flowing the cleaning water from inside the equipment During this cleaning process, the dividing and loading pipette 42 is placed immediately above a trough 43 in a cleaning position i A sample adhering to the outside surface of said dividing and loading pipette 42 is cleaned in the same position in accordance with

The composition described above.

  The stirring device B 2 comprises, as shown in FIG. 8, an agitating arm 50 having a shape substantially in

  L plan, a stirring body 51 arranged in an intermediate portion

  diary of said agitator arm 50, and a body supporting a drain pipette 60 rotatably supported by a top portion of said

agitator arm 50 via a motor 52.

  One end of the agitator arm 50 of said agitation device B 2 is rotatably supported by a shaft 40 which supports the pipette arm 41 of said third pipette device P 4. The agitation body 51 comprises an agitation rod

  (not glossy) driven in rotation by a motor 54.

  It is evident from FIG. 8 that the drain pipette device Hi comprises said drain pipette support body 60 whose shape p Lane is a long hoop, said motor 52 provided on the lower surface of the portion of above said agitator arm 50, a rotation shaft 55 of the motor 52 and a drain pipette 61 fixed to the other end of the drain pipette support body 60 Said drain pipette support body 60 can rotate freely around L When said motor 52

is working.

  The drain pipette 61 operates in such a way that it sucks in and rejects the magnetic solution insoluble in the antibody of said reaction container 1 while said magnetic body M1 still adsorbs the magnetic body insoluble in the antibody m in the container 1 on the inner surface of the reaction vessel 1 in a position located in front of the position g for dividing and loading the enzyme-labeled antibody solution. Thus, in the normal state, the drain pipette 61 is mounted supported, with a long axis xl of the pipette perpendicular to an axis yl of the top portion of the agitator arm 50 so that the drain pipette 61 is positioned immediately above the reaction vessel 1

  or of a trough 44 of the cleaning position i.

  Consequently, the drain pipette support body is pushed by the pipette arm 41 of said third pipette device P 4 when this third pipette device P 4 rotates from the position of the trough 43 to the position d d aspiration of enzyme labeled antibody, as shown in

  Figure 9 (C) Thus, the body 60 rotates in the direction of the acute L-

  The dimensions of a watch in FIGS. 9 (A) to 9 (C) with a support axis of the rotation shaft 55 of said motor 52 IL is thus laced so that the long axis xl Line on yl axis of

  The top portion of the agitator arm 50.

  As a result, the dividing and loading pipette 42 of said third pipette device P 4 rotates in the aspiration position of the so Lution of enzyme-labeled antibody without being hindered by said drain pipette support body 60 At this time, the rotation shaft 55 of said motor 52 is pushed by the pipette arm 41 of the third pipette device P 4 since a switch for the motor (not glossy) is in the stop position. When the dividing and loading pipette 42 of the third pipette device P 4 draws up a predetermined quantity of La so Lution of enzyme-labeled antibody from the reagent container 6 in the suction position of La so Lution antibody labeled with an enzyme and returns to said position of the cleaning gauge, the long axis xl of said drain pipette support body 60 remains on the same straight line as the axis yl of the top portion of the agitator arm 50 until the dividing and loading pipette 42 of the third pipette device P 4 is p Laced in The initial position (The position shown in FIGS. 9 (A) and (B)) After the dividing pipette and loading 42 of the third pipette device P 4 is p Laced in The initial position Le, The motor 52 is started since a detector or switch device (not i L Glossy) has detected The return to this position, resulting in insi en rotation Said drain pipette support body 6 in the initial position Le (The lacquer position L Le The yl axis of the top portion of the agitator arm 50 becomes perpendicular to the Long axis xl) The motor switch 52 is then turned to the stop position after the completion of these working methods L, the pipette arm 41 of the third pipette device P 4, the agitator arm 50 of the stirring device B 2 and the support body of the drain pipette 6 of the Hi drain pipette device are rotated together to the position shown in Figure 9 (A) and placed immediately above each container

reaction 1.

  Said stirring device B 2 can also be composed so that air bubbles are blown in for stirring in place of said stirring rod In addition, the motor 52 can also be eliminated by replacement by means of a spring etc which can replace the support body

drain pipette 6.

  Said stirring devices B1 to B 6 including said stirring device B 2 are composed in such a way that the sample in the reaction container 1 which is located upstream of an angular step corresponding to each container in the current dividing and charging position either agitated by a stirring rod or by air bubbles These devices and tools are composed so that each pipette is cleaned at each pipette cleaning position h, i, j, k , m and N after

process mentioned above.

  A predetermined amount of the enzyme labeled antibody solution was divided and loaded into the reaction container 1 from the reagent container 6 in the g position of dividing and loading the antibody solution

  labeled with an enzyme and then stirred as described above.

  After these processes, the reaction vessel 1 with said solution

  of antibody labeled with a divided and charged enzyme is trans-

  brought to the next position q o is a magnetic body M 2 As soon as the reaction vessel 1 arrives in this position q, said magnetic body M 2 is excited to adsorb the magnetic body m insoluble in the antibody in the container

  reaction 1 on the inner surface of said reaction container 1.

  In addition, ingredients other than the magnetic body m insoluble in the antibody are drained via the cleaning and stirring device Gi. A cleaning solution W is then fed into the reaction vessel 1, stirred in the following position

  and transported to the rejection position r of the sample.

  When the reaction container 1 arrives in the rejection position r after the completion of the stirring work L, said magnetic body M 3 is excited to adsorb the magnetic body m insolub Le in the antibody in the reaction container 1 on the surface of the inner wall of said reaction vessel 1 At the same time, the ingredients other than the magnetic body m inso Lub Le in the antibody in the sample L Lon are drained via the cleaning and stirring device G 2 , while feeding a cleaning solution W into the reaction vessel 1 The reaction vessel is then subjected to a stirring process in the next position and then transported to the reject position t

  of the sample L Lon When the reaction vessel 1 thus comp Lè-

  The agitated body is transported and arrives in the rejection position t, the said magnetic body M 4 is excited to adsorb the magnetic body m inso Lub Le in the antibody in the reaction container 1 on the surface of the inner wall of said container. reaction 1 At the same time, ingredients other than the magnetic body m inso Lub Le in the antibody in the sample L Lon are drained via the cleaning and stirring device G 3 while supplying a cleaning solution W in The container of

  reaction 1 which is stirred in the next position.

  The magnetic bodies M 2 to M 5 Loca Lized in each position q, r and t are composed in the same way as Said body

  magnetic Ml, and so we do not give here a description p Read

detai LLée.

  Said cleaning and stirring devices Gi to G 3 arranged in each position q, r and t are composed as shown

in Figures 10 and 11.

  P Read more explicitly, each of the cleaning and stirring devices Gi to G 3 comprises an L-shaped arm p Lan 71, one end of which is fixed to the shaft 70, a so-called suction suction pipette 72 mounted at the top portion 71 has arm 71, a pipette supplying cleaning water 73 and a stirrer body 74. Arm 71 is controlled to lift and rotate in rotation by a non-glossy drive device which drives the shaft 7 which is fixed on one end of the arm, in the same way as for the conventional pipette mechanism known from the prior art. Thus, the arm 71 is composed in such a way that it alternately transports said arm. OS solution suction pipette 72, water supply pipette 73 for cleaning water

  and the stirring body 74 between an immediately understood position

  above each corresponding reaction vessel 1 and

  immediately above the cleaning troughs 75, 76.

  The solution suction pipette 72 sucks and rejects a sample in a reaction vessel 1, and is connected to and

  communicates with a pump (not shown).

  The cleaning water supply pipette 73 supplies the cleaning water to a reaction vessel 1, the upper end of which is connected to and communicates with the pump and a tank.

  cleaning water (not shown).

  The stirring body 74 comprises, as shown particularly

  in FIG. 11, a stirring rod 78 fitted with stirring blades at the lower end and a motor 77 for rotating the stirring rod 78 Of course, in place of the stirring rod 78 , The stirrer body 74 can also

  understand a pipe that provides air bubbles.

  Thus, the compound solution suction pipette 72, the cleaning water supply pipette 73 and the stirring body 74 are installed sequentially from downstream in the direction of transport of the reaction vessels 1 which are there. inserted Since the solution suction pipette 72, the

  cleaning water supply pipette 73 and stirred body

  tion 74 are arranged sequentially from downstream in the direction of transport of the reaction vessels 1, the magnetic bodies m insoluble in the antibody in the reaction vessels 1 are adsorbed on the surfaces of the internal walls of the reaction vessels 1 to 1 using magnetic bodies M 2 to M 5 at each solution suction position, the suction and rejection of the remaining samples not necessary only is done using the pipettes 72 for solution suction and the water of

  W cleaning are fed into each of the reaction vessels.

  After that, the cleaning waters W and the magnetic bodies m insoluble in the antibody are agitated by the stirring rod 78 to complete the cleaning of the magnetic bodies m inso Lubles in

  the antibody quickly and efficiently.

  When a job using the solution suction pipette 72, the cleaning water supply pipette 73 and the stirring body 74 is finished as described above, said arm 71 is rotated in the direction of the cleaning troughs 75, 76 by said drive device while the solution suction pipette 72 and the stirring body 74 are positioned immediately above the cleaning troughs 75 and 76 respectively The pipettes 72, 73 and the stirring body 74 are cleaned by each cleaning device structured in the same way as a conventional cleaning mechanism known in the prior art After completion of such work as described above, said pipette d solution 72, the cleaning water supply pipette 73 and the stirrer body 74 are transported again immediately above the containers

  These procedures are repeated to process the samples.

  Ions in reaction vessels 1 sequentially.

  As described above, cleaning the magnetic bodies

  m ticks insoluble in the antibody is done in three steps, resulting in a more complete cleaning effect while avoiding cross contamination However, the number of these cleaning steps can also be freely set in accordance with

  functions of the applied automatic analysis device.

  After the completion of the cleaning of the magnetic bodies insoluble in the antibody in the manner described above, said reaction vessels are transported to a position

rejection of samples.

  As soon as a reaction container 1 arrives in this sample rejection position u, said magnetic body M 5 is excited to adsorb the magnetic body m insoluble in the antibody in the reaction container 1 on the surface of the wall interior of said reaction container 1 At this time, ingredients other than the magnetic body m insoluble in the antibody are drained via the drain pipette device H 2. Next, a stroma solution 7 is fed into the reaction container 1 via the fourth pipette device P 5 and, in the following position, it is stirred by a stirring device B 3, and then, in the position after the next, a reaction stop solution is divided and loaded into the

  reaction vessel 1 via a fourth pipette device P 6.

  A plurality of types (for example 4 types in the illustrated embodiment) of reaction stop solutions are housed in reagent bottles 8 which are supported by a reagent holder 80 composed of a preferred material for viewing and controlling reagent volumes from the outside, for example a

  transparent glass or reinforced resin.

  The reagent holder 80 is constructed according to a planar arc shown in FIG. 1 Each of said reagent bottles 8 is inserted and held in each holding hole whose axis is formed at a predetermined pitch relative to the center of rotation of said fourth device pipette P 5 In addition, at the top portion of said reagent holder 80, cleaning troughs 82, 83 are

fully assembled.

  The types of reaction stop solution, divided and loaded into the reaction vessels 1 as soon as they arrive in the position for dividing and loading the reaction stop solution, enter a control device (not illustrated), beforehand The fourth pipette device P 5 selects a reagent bottle 8 in which the specified reaction stop solution is housed, from among the other reagent bottles 8 The pipette device P 5 draws up a predetermined quantity of the solution of reaction stop from the selected reagent bottle 8, and then divide and load the reaction stop solution drawn into the reaction container 1 At this time, it is preferable that these reagent holders 80 are arranged on the front side of the automatic analysis device in consideration of the

  easy replacement of reagent bottles 8.

  Furthermore, the fourth pipette device P 5 comprises, as in a conventional reagent pipette L Le known from the prior art, an arm 84 one end of which is supported by a shaft, a pipette 85 fitted at the other end of the arm 84, a pump (not glossy) which is connected to and which communicates with the pipette 85 and draws a predetermined quantity of a reaction stop solution and discharges it into the reaction vessel 1 and each device drive (not glossy) which controls said arm to rotate it from one position

  predetermined in another position if a predeter timing

  mined and to Leave the arm has L Ler up and down in

each position.

  The measurement using pipette 85 is made as follows.

  Water is charged to a suction system while the reaction stop solution and water are drawn in and measured by separation of the two from each other via air only the stop solution reaction vessel is then discharged, after which the interior of the pipette is cleaned by passing cleaning water inside. During this cleaning operation, the fourth pipette device P 5 is placed immediately above L cleaning trough 82, o a sample adhering to the external surface of said fourth pipette device P 5 is cleaned in

The same position.

  The stirring device B 3 is transported taking into account

  of the rotation of the arm 84 of said fourth pipette device P 5.

  When the fourth pipette device P 5 is dividing and loading a reagent into the reaction container 1, a stirring rod or air bubbles from the stirring device B 3 shake the sample in the container reaction 1 positioned

  downstream of the division and loading position of an angular step

  reaction vessel sample The sample adhering to the outer surface of said stirring rod or said tube

  air bubbles is cleaned in the same position.

* The reaction vessel 1, in which an enzymatic reaction was stopped by the reaction stop solution 8,

  is then transported to an optical measurement position s.

  When the reaction vessel 1 arrives in this position s,

  Said magnetic body M 6 is excited to attract The magnetic body

  as m insoluble in the antibody in the reaction vessel 1 in the lower part of the inner wall of said reaction vessel 1 so that it does not obstruct by the optical passage f of a measurement light beam coming from a measuring device

optics 9.

  The optical measuring device 9 comprising a detection unit or an observation point, measures the sample colorimetrically in the reaction vessel 1 according to the end point method using light of wavelength 400 nm and 600 nm chosen by the length conversion system

wave using a filter.

  Measurement data, obtained at an optical measurement position 9 is processed in accordance with the method corresponding to conventional optical measurement systems and indicated on an indication device which is not illustrated. In addition, said data

  are stored in a printed circuit storage card.

  Furthermore, each of said mechanisms is driven and controlled by a conventional printed circuit card which can be read or written in a manner known in the prior art, although

it is not illustrated.

  These circuit board storage cards and these circuit board drive cards are provided with

  integrated circuits from which data can be read.

  These integrated circuits include an electrically erasable programmable read-only memory (EEPROM). In addition, the integrated circuits also incorporate drive and control means corresponding to the analysis articles operated in a relevant installation, in a group. In addition, the cards store also

  names, numbers of registrations, states, affiliations

  and other operational information regarding

  operators allowed to use the relevant analytical device.

  In addition, the reaction vessels 1 are trans-

  worn in a cleaning device F after the completion of an optical measurement job This cleaning device F empties all the L Lons samples into the reaction vessels 1 In addition, the reaction vessels are cleaned in several stages up to the interior of the reaction vessels 1 becomes reusable, using cleaning water The composition of the cleaning device F is the same as that of the devices

  multi-stage cleaning process known publicly Therefore

  quent, a more detailed description is not given here.

  In figure 1, the symbol t shows a position for cleaning the pipettes of a sampling pipette device

P 1.

  The magnetic body m insoluble in the antibody is sensitized on conventional fine magnetic particles known in the prior art under the name of antibodies.

  magnetic M 1 to M 6 adsorb these magnetic bodies m insolu-

  in the antibody on the interior surfaces of the reaction vessels 1 and include electromagnets or permanent magnets and are arranged in the rejection position p, q, r, t and

  u of said samples and in the optical measurement position S.

  The operation of the embodiments in the

  configuration described in detail above is as follows.

  First, put the main switch (not shown) in the on position while placing the device's printed circuit board in the automatic immunity analysis device A which has been set. in the state

  Analyzable Thus, each mechanism is set in the analyzed state.

  ble while The details analyzed are indicated on an indication device (not illustrated) such as a CRT In this step, the operator selects a group of preferred analyzes by pressing the article switch or the group of selective switches (not illustrated) for a relevant examination object referring to the indication of the indication device, to bring a unit

  analysis to be carried out in accordance with said selected analysis articles

  tionnés. Then, when a start switch (not shown) is turned on in the step mentioned above, the sample cassette 12 transports each sample container

  in position b of sample suction L Lon, inter-

  mittent, lacquered L Le The sample pipette device L Lonnage Pl

  draws a sample L Lon Then, said sample pipette device

  ti L Lonnage Pl is rotated to divide and load the sampled L Lon drawn into the reaction vessel 1, in an amount for example of 10 100 µm After completion of the above mentioned work, the reaction vessels 1 are driven in rotation by a angular displacement Laire corresponding to 71 containers (3550) in the opposite direction of the acute L Les of a watch in FIG. 1, and stopped As a result, said reaction vessels 1 are transported intermittently d an angular step Laire of a reaction vessel in the acute direction L Les of a watch in

  Figure 1 After this La, The reaction vessels 1 are trans-

  worn sequentially Lement and intermittently in inter-

  va L de la Langing angu Laire corresponding to each container of

  Reaction clockwise L clockwise in Figure 1. When the reaction vessels 1 are powered from the position

  sample Lonnage "a" to the position e for dividing and loading The magnetic solution insoluble in the antibody, the magnetic solution insoluble in the antibody is divided and loaded into each reaction vessel 1 to using a first pipette device P 2 In the following position, the solution is stirred by the stirring device B 1 After this step, a cleaning solution 5 is divided and loaded into

  each of the reaction vessels 1 in position f.

  The reaction vessels 1 containing the additionally divided and charged cleaning solutions 5 are transported to a position po the first magnetic body M 1 is arranged and, when the reaction vessel 1 arrives in said position p, this first magnetic body M 1 is excited to adsorb the magnetic body m insoluble in the antibody in the reaction vessel 1 on the surface of the interior wall of said vessel

  In addition, ingredients other than the magnesium

  tick m insoluble in the antibody are drained via a device

with drain pipette H 1.

  When this work is completed with the reaction vessels, the vessels are then transported to the position g for dividing and loading the so Lution of enzyme-labeled antibodies or a so Lution of stroma, the so Lution d antibody labeled with an enzyme is divided and loaded via a

  third pipette device P 4 of a predetermined amount.

  In the following position, the so Lution in the container of

  reaction 1 is stirred by a stirring device B 2.

  The reaction vessels 1, thus loaded with so Lution of stroma, that is to say The so Lution of antibody marked by an enzyme after division, are transported to the following position qo The magnetic body M 2 is p Laced When The container Reaction 1 arrives in said position q, Said magnetic body M 2 is excited causing the magnetic body to adsorb m inso Lub Le in The antibody in Reaction vessel 1 on The surface of The

  inner wall of said reaction vessel 1 Read more, samples

  ti L Lons other than The magnetic body m inso Lub Les in Anti-

  bodies are emptied After this, a so Lution cleaning W is fed into the reaction vessel 1 In the following position, the so Lution W is agitated while transporting the reaction vessels in the position r of rejection of

The L Lon sample.

  The reaction vessels 1, thus completely agitated, are transported to the rejection position r and, when the reaction vessels arrive in said position r, the said magnetic body M 3 is excited and causes the magnetic body to be absorbed m inso Lub Le in L antibody in reaction vessel 1 on the surface of the inner wall of said reaction vessel 1 More, samples L other than the magnetic body m inso Lub Les

  in the antibodies are drained, after which a so Lution of net-

  toyage W is supplied to the reaction vessels 1 In the following position, the reaction vessels are agitated and

  then transported to a rejection position of L Lhant.

  When reaction vessels 1, after being

  completely shaken in the manner described above, are trans-

  brought to the rejection position t and arrive at this position, the said magnetic body M 4 is excited, causing the magnetic body to m adsorb in the antibody in the reaction vessel 1 on the surface of the inner wall of the said vessel

  reaction 1 In addition, Lons samples other than the magneti-

  that m insoluble in the antibody are drained After this step, a cleaning solution W is supplied to the reaction vessel 1 and, in the following position, the solution W is agitated and then the reaction vessels are transported to the position u rejection of the sample When the reaction vessels 1 thus completely agitated are transported to a rejection position u and arrive there, said magnetic body M 5 is excited causing the magnetic body m insoluble in the antibody to adsorb in the reaction vessel 1 on the surface of the

  inner wall of said reaction vessel 1 Thus, samples

  furrows other than the magnetic body m insoluble in the anti

  bodies are drained via the H 2 discharge pipette device.

  After this, a stroma 7 solution is fed into the

  reaction vessel 1 via The fourth pipette device P 5.

  The solution 7 is stirred in the following position using a stirring device B 6 In the position after the following, a reaction stop solution 8 is divided and loaded into the

  reaction vessel 1 via a fifth pipette device P 6.

  The reaction vessels 1, in which an enzymatic reaction has been stopped by the reaction stop solution 8 in the manner described above, are transported to an optical measurement position and, when the reaction vessels 1 arrive in this position s, said magnetic body M 6 is excited, causing adsorption of the magnetic body m insoluble in the antibody in the reaction vessel 1 on the lower side of the interior wall of said reaction vessel 1 so that a passage

  optics f for a measurement light beam from the available

  Optical measurement device 9 remains unobstructed.

  Thus, data measured by the optical measurement device 9 is processed and calculated in accordance with said methods and indicated on an indication device not shown. Furthermore, said data is stored in a storage card with printed circuit. Furthermore, the containers of reaction 1 having passed

  completely through the optical measurement work are trans-

  carried in a cleaning device F which empties all the samples L Lons from the reaction vessels 1 In addition, the reaction vessels 1 are cleaned by the cleaning water in stages

  multiple times until the containers can be reused.

  In the previous embodiment, a composition for activating the automatic analysis apparatus for immunity A controlled by a printed circuit starting card was used for the explanation. However, the present invention is not not limited only to such a composition but is also applicable to an activated automatic immunity analyzer

  by another control means known from the prior art.

  In this embodiment, the cleaning solution 5 is divided and loaded in position f using the second pipette device P 3 and then, in position p, the first magnetic body M 1 is excited to adsorb the magnetic body m insoluble in the antibody on the surface of the wall

  inside the reaction vessel 1 together with the samples

  Drainage voids other than the magnetic body m insoluble in the antibody, using the drain pipette device H 1 according to a two-step method used in the apparatus for automatic analysis of immunity-A, as an example However , the present invention is not limited to this type of arrangement either. Instead, an apparatus for automatic analysis of Immunity A in a single-stage system can also be realized, that is, i.e. a stroma solution, i.e. an enzyme labeled antibody solution is divided and loaded into position g after the division and stirring work of the magnetic solution is completed insoluble in the antibody,

  by omitting said two-step process.

  According to the present invention, as described

  in detail above, an insoluble antibody in which an anti

  body is fixed on fine magnetic particles is used

  in the measurement of enzyme immunity using the EIA method.

  Therefore, the time required to clean said antibody can be greatly simplified and shortened. As a result, the duration of this inspection can be reduced significantly while

  that the total automation of a series of works such as sampling

  lonnage, division and loading of a reagent, agitation, cleaning and measurement, is ensured Thus, the present invention provides a completely new and excellent automatic immunity analysis device, better than the conventional devices known from the prior art since the invented device provides a

  complete automation of these types of inspections.

Claims (4)

  1 An automatic immunity analysis device, characterized in that it comprises reaction vessels (1) arranged in series, a transport device for said reaction vessels, a first dividing device (P 1) which sucks a sample (10) in a predetermined quantity in a predetermined position and which divides and loads said sample into each of said reaction vessels, a first stirring device (P 2, B 1) which divides and loads a magnetic solution insoluble in l 'antibody in each of said reaction vessels containing said sample in divided and loaded state, a second dividing device (P 4) which is provided after said first stirring device and which divides and loads a stroma solution in each of said reaction vessels, an absorption device (M 1) which adsorbs said magnetic solution insoluble in the antibody on a surface of the inner wall of cha each of said reaction vessels, a first cleaning device (P 3) which rejects a reaction solution contained in each of said reaction vessels while said magnetic solution insoluble in the antibody is still adsorbed on the inner wall of each of said reaction vessels reaction, and which then cleans each of said containers, a second stirring device (B 2) which divides and shakes an enzyme-labeled antibody solution, a second adsorption device (M 2) which adsorbs said magnetic solution insoluble in the antibody on the surface of the interior wall of each of these reaction vessels, a second cleaning device (G 2) which rejects a reaction solution contained in each of these reaction vessels while said magnetic solution is insoluble in the antibody is still adsorbed on the inner wall of each of said reaction vessels and which then cleans each said containers, a third dividing device (P 6) which divides and loads a reaction stop solution, a measuring device (9) which optically measures a sample in each of said reaction containers and in an optical measurement position, and a third cleaning device (F) which cleans the interior of each of said reagents   reaction after completion of a measurement.   2 The automatic immunity analysis apparatus according to claim 1, characterized in that said first stirring device for the magnetic solution insoluble in the antibody comprises a reagent container holder (1-1) which is driven in rotation by a drive apparatus (22), a rotary body (21) which is engaged with a retention hole of said reagent container holder in a freely rotatable manner, a stationary gear body (25) on the surface peripheral of which are cut into gear teeth, a gear body (24) which engages the gear teeth of said fixed gear body and which drives said rotary body when said reagent container holder is driven rotation and   projecting bodies (26) which are raised at predetermined intervals   mined along a peripheral surface of said gear body   fixed, and in that a magnetic solution insoluble in the anti   body housed in said rotary body is rotated and agitated when said reagent container holder is rotated, and housed in said rotary body in such a way that said magnetic solution insoluble in the antibody is shaken and   agitated by one of said projecting bodies.   3 The apparatus L for automatic analysis of immunity according to claim 1, characterized in that said first stirring device which divides and charges a magnetic solution insoluble in the antibody contained in each of said reagent containers in each of said reaction vessels comprises an agitator arm (50) and a pipette arm (41), said agitator arm is equipped with one of said agitation bodies (51) in an intermediate portion and with a drain pipette supported by a portion from above and having the shape of a flat L, and said pipette arm is equipped with a dividing pipette with a terminal portion, while said agitator arm and said pipette arm are supported coaxially; and that said stirring rod, said drain pipette and said dividing pipette are cleaned in a predetermined position; only said dividing pipette is rotating while pushing the drain pipette and moves to a solution suction position; and said emptying pipette returns to its place when said dividing pipette draws up the insoluble magnetic solution in   The antibody returns to said cleaning position.   4 The automatic immunity analysis device according to claim 1, characterized in that said first and second cleaning devices for cleaning the interior walls of said reaction vessels comprise an L-shaped arm (71) fixed on a shaft ( 70) at one end, a solution suction pipette (72) mounted on a top portion (71 a) of said arm, a pipette (73) supplying the cleaning water and a stirrer body (74); and in that said solution suction pipette, said cleaning water supply pipette and said agitation body are mounted on a top portion of said arm in sequential order from the downstream side to the upstream side in the direction of transport of the reaction vessels in which said pipettes and said body of agitation are inserted.